Method of optimizing the treatment of proliferative diseases mediated by the tyrosine kinase receptor kit

Abstract

The invention relates to a method of treating proliferative diseases mediated by the tyrosine kinase receptor KIT, in particular GIST, in a human patient population.

1 . A method of treating a proliferative disease mediated by the tyrosine kinase receptor KIT in a human patient comprising the steps of
 (a) administering a predetermined fixed amount of Imatinib or a pharmaceutically acceptable salt thereof to the human patient suffering from such a disease,   (b) collecting at least one blood sample from said patient within the first 12 months of treatment,   e.g. within the first 30 days,   (c) determining the plasma trough level (Cmin) of Imatinib, and   (d) adjusting the dose of Imatinib or a pharmaceutically acceptable salt thereof in a manner that a Cmin of at least about 1100 ng/mL of Imatinib is achieved in said patient.   
     
     
         2 . Method according to  claim 1  wherein the dose of Imatinib or a pharmaceutically acceptable salt thereof is adjusted in a manner that a Cmin between about 1100 and about 2500 ng/mL of Imatinib is achieved in said patient. 
     
     
         3 . A method of treating GIST in a human patient comprising the steps of
 (a) administering a predetermined fixed amount of Imatinib or a pharmaceutically acceptable salt thereof to the human GIST patient in need thereof,   (b) collecting at least one blood sample from said patient within the first 12 months of treatment,   (c) determining the plasma trough level (Cmin) of Imatinib, and   (d) adjusting the dose of Imatinib or a pharmaceutically acceptable salt thereof in a manner that a Cmin of at least about 1100 ng/mL of Imatinib is achieved in said patient.   
     
     
         4 . Method according to  claim 3  wherein the dose of Imatinib or a pharmaceutically acceptable salt thereof is adjusted in a manner that a Cmin between about 1100 and about 2500 ng/mL of Imatinib is achieved in said patient. 
     
     
         5 . Method according to  claim 3  wherein Imatinib mesylate is administered. 
     
     
         6 . Method according to  claim 3  wherein in step (a) a daily dose of between about 200 and about 800 mg of the monomesylate salt of Imatinib is administered orally. 
     
     
         7 . Method according to  claim 3  wherein in step (a) a daily dose of about 400 mg of the monomesylate salt of Imatinib is administered orally. 
     
     
         8 . Method according to  claim 3  wherein the at least one blood sample is collected within the first 3 months of treatment. 
     
     
         9 . Method according to  claim 3  wherein the at least one blood sample is collected within the first 30 days of treatment. 
     
     
         10 . Method according to  claim 3  wherein the exon 11 KIT mutation is observed in the GIST patients treated. 
     
     
         11 - 14 . (canceled)